Diffuse Optical Imaging (DOI) allows us access to the hemodynamic response in tissue. It has been shown that we can, by detecting the effects of neuro-vascular coupling, relate this to functional events in the brain. Existing technologies in DOI are limited by a number of factors, but most strongly by the absence of viable clinical applications where they may be applied. In this project we are targeting veterans (at the upper end of the pediatric population) with penetrating Traumatic Brain Injury (TBI) and Autistic Spectrum Disorder (ASD) patients. These patients are low-functioning and typically pediatric populations. Over the course of the 2011 fiscal year we have secured a Bench to Bedside grant to fund the latter study and extended the funding for the former study under the Center for Neuro-Rehabilitative Medicine. We have again had several presentations accepted at the Society for Neuroscience and have several key papers in submission on our various projects. We have completed the development of our fiber based instrument and are finishing assembling a second instrument through our collaborators at Drexel). We have commenced studies using instruments at our lab and at our other collaborators lab in Georgetown. The latter is a DOI instruments combined with EEG. Clinically we are continuing testing with healthy volunteers and have some initial data from TBI subjects. We have an in-place IRB through NICHD to test our prototype systems here at NICHD for both projects including a neuropsychological evaluation. Alongside our tests for cognitive tasks (event complexity judgment task, a verbal working memory task, and a multi-task) we have further developed an approach for resting state and functional connectivity. For the resting/functional state connectivity existing techniques such as correlation and data-driven decompositions, for assessing functional connectivity, generally assume temporal stationary for the brain signals over the duration of the recording. Such an assumption would result in not detecting the dynamic changes that exist in functional connectivity between engaged regions of the brain. We have been investigating time-frequency analysis techniques to capture the dynamic behavior of connectivity across the prefrontal cortex, at both resting-state and task-based experiments. With the inclusion of neuropsychological evaluation we are well on our way to providing the basis for our ASD study, once complete we will be able to use the existing data from NIMH to identify a patient cohort to closely match our healthy subject population. Theoretically we are currently finishing the development of techniques to handle the shortcomings of current DOI techniques. We have identified an approach using stereotactic imaging that allows us to co-register our optical data to the MNI atlas with accuracy matching that of similar MRI experiments. Currently this requires the existence of a patient specific MRI and our focus is on the ability to remove this requirement as this may not be available for our target patient populations. Initial results have also been done on developing novel techniques to accelerate optical image reconstruction. Currently techniques for 3 dimensional imaging of optical data require days or at best hours to reconstruct by expert users. We are developing novel approaches using a combination of our atlasing approach and analytical functions to address both these issues with DOI. Our collaboration with NINDS has fully developed a fiber based imager which has added to our array devices for comparison and contrast of DOI techniques. This particular system has also increased the areas of the brain accessible to our devices expanding us away from the prefrontal cortex to include motor and visual cortices. Also we have a fully miniaturized system under development in association with our collaborators at Drexel. Initial designs for optical transmitter and receiver have been implemented and the functionality of each module has been verified experimentally. Quad vertical cavity surface emitting laser diodes are used in the transmitter, and the system takes advantage of Gradient-Index (GRIN) lens technology to achieve excellent optical collection efficiency. We are currently working on the integration of the modules. These projects will combine to produce fully wearable DOI for Near Infrared functional imaging. Our theoretical research is also examining motion artifact as a signal instead of noise. Initial results suggest that if we can model the motion of our imaging system relative to the subject via the helmet interface (a process being worked on by our instrumentalists), we should further be able to enhance optical signals to an unprecedented level of accuracy and quantitation in the field. The final part of the brain project involves structural imaging. We have developed a novel approach to detect hematomas in a rapid handheld device. This approach would greatly help for the triaging for the presence of hematomas and greatly increase the efficiency of use of more expensive limited access technologies such as CT or MRI. Theoretical results indicate the device will work to detect Dural hematomas and also that the potential to map them with a simple handheld device exists. Such a device could be critical to aiding in surgical interventions where CT or MRI is unavailable. The approach being developed has undergone initial testing with a prototype imager on phantoms and initial results suggest that the more sources and more detectors at higher density paradigm for better near infra-red imaging may not be correct. In fact it may be possible to achieve faster structural imaging of similar quality with smaller devices. Unfortunately such approaches cannot be applied to functional imaging.